Ethanol exerts a dose-dependent stimulatory or inhibitory effect on the CNS; however the mechanism of these effects is not clear. Ethanol alters the action of several central acting GABA-ergic drugs, such as benzodiazepines or barbiturates, which suggests that ethanol interacts with GABA receptors. Ethanol exerts a biphasic effect on the binding of muscimol (GABA-A agonist) to GABA receptors in syanaptosomal membranes obtained from different brain regions. Muscimol binding is inhibited at concentrations of ethanol ranging from 1.5 mM to 6 MM, whereas, it is enhanced at higher concentrations. Decreased muscimol binding in the presence of low levels of ethanol was due to reduced ligand affinity of the GABA receptors, whereas, enhanced muscimol binding at high ethanol concentrations was due to increased receptor number. Glucocorticoids also appear to act directly on central GABA receptors, but in a dose-dependent manner opposite to that of ethanol. Nanomolar levels of glucocorticoids enhance muscimol binding, whereas, micromolar levels inhibit binding. These effects are due to increased receptor affinity for the ligand and a decreased receptor number in the presence of low or high levels of glucocorticoids, respectively. In the CNS there exist a complex interaction between ethanol, glucocorticoids and GABA receptors. Since low concentrations of ethanol reduce steroid binding to brain membranes, it is possible that in the presence of low levels of ethanol, reduced glucocorticoid binding may in part decrease muscimol binding. The possible interaction of alcohol, glucocorticoids and GABA receptors in the CNS in Alcoholic Cushing's Syndrome (elevated cortisol) may explain the symptoms of hypocortisolemia.